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Serum Complement C3 and C4 and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression.

ABSTRACT: Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to investigate possible differences in the serum concentrations of two routinely measured complement components, C3 and C4, in COVID-19 patients with different severity and survival status. We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum complement C3 and C4, measures of COVID-19 severity, and survival. Eligibility criteria were a) reporting continuous data on serum C3 and C4 concentrations in COVID-19 patients, -b) investigating COVID-19 patients with different disease severity and/or survival status, c) adult patients, d) English language, e) ≥10 patients, and f) full-text available. Using a random-effects model, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated to evaluate differences in serum C3 and C4 concentrations between COVID-19 patients with low vs. high severity or survivor vs. non-survivor status. Risk of bias was assessed using the Newcastle-Ottawa scale whereas publication bias was assessed with the Begg's and Egger's tests. Certainty of evidence was assessed using GRADE. Nineteen studies in 3,764 COVID-19 patients were included in the meta-analysis. Both C3 and C4 concentrations were significantly lower in patients with high disease severity or non-survivor status than patients with low severity or survivor status (C3 SMD=-0.40, 95% CI -0.60 to -0.21, p<0.001; C4 SMD=-0.29, 95% CI -0.49 to -0.09, p=0.005; moderate certainty of evidence). Extreme between-study heterogeneity was observed (C3, I² = 82.1%; C4, I² = 84.4%). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. There was no publication bias. In meta-regression, the SMD of C3 was significantly associated with white blood cell count, C-reactive protein (CRP), and pro-thrombin time, whereas the SMD of C4 was significantly associated with CRP, pro-thrombin time, D-dimer, and albumin. In conclusion, lower concentrations of C3 and C4, indicating complement activation, were significantly associated with higher COVID-19 severity and mortality. C3 and C4 might be useful to predict adverse clinical consequences in these patients. Systematic Review Registration: PROSPERO, Registration number: CRD42021239634.

SUBMITTER: Zinellu A

PROVIDER: S-EPMC8215447 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting total, HDL, and LDL-cholesterol, and triglyceride concentrations in hospitalized patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January 2020 and January 2021, for studies describing lipid concentrations, COVID-19 severity, and survival status (PROSPERO registration number: CRD42021253401). Twenty-two studies in 10,122 COVID-19 patients were included in the meta-analysis. Pooled results showed that hospitalized patients with severe disease or non-survivor status had significantly lower total cholesterol (standardized mean difference, SMD = -0.29, 95% CI -0.41 to -0.16, p < 0.001), LDL-cholesterol (SMD = -0.30, 95% CI -0.41 to -0.18, p < 0.001), and HDL-cholesterol (SMD = -0.44, 95% CI -0.62 to -0.26, p < 0.001), but not triglyceride (SMD = 0.04, 95% CI -0.10 to -0.19, p = 0.57), concentrations compared to patients with milder disease or survivor status during follow up. Between-study heterogeneity was large-to-extreme. In sensitivity analysis, the effect size of different lipid fractions was not affected when each study was in turn removed. The Begg's and Egger's t-tests did not show evidence of publication bias, except for studies investigating LDL-cholesterol. In meta-regression, significant associations were observed between the SMD of LDL-cholesterol and age and hypertension, and between the SMD of triglycerides and study endpoint and aspartate aminotransferase. In our systematic review and meta-analysis, lower total, HDL, and LDL-cholesterol, but not triglyceride, concentrations were significantly associated with COVID-19 severity and mortality. Cholesterol concentrations might be useful, in combination with other clinical and demographic variables, for risk stratification and monitoring in this group. Systematic Review Registration: PROSPERO registration number: CRD42021253401.

Project description:BackgroundObesity affects the course of critical illnesses. We aimed to estimate the association of obesity with the severity and mortality in coronavirus disease 2019 (COVID-19) patients.Data sourcesA systematic search was conducted from the inception of the COVID-19 pandemic through to 13 October 2021, on databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned.Study selection and data extractionFull-length articles focusing on the association of obesity and outcome in COVID-19 patients were included. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for study selection and data extraction. Our Population of interest were COVID-19 positive patients, obesity is our Intervention/Exposure point, Comparators are Non-obese vs obese patients The chief outcome of the study was the severity of the confirmed COVID-19 positive hospitalized patients in terms of admission to the intensive care unit (ICU) or the requirement of invasive mechanical ventilation/intubation with obesity. All-cause mortality in COVID-19 positive hospitalized patients with obesity was the secondary outcome of the study.ResultsIn total, 3,140,413 patients from 167 studies were included in the study. Obesity was associated with an increased risk of severe disease (RR=1.52, 95% CI 1.41-1.63, p<0.001, I2 = 97%). Similarly, high mortality was observed in obese patients (RR=1.09, 95% CI 1.02-1.16, p=0.006, I2 = 97%). In multivariate meta-regression on severity, the covariate of the female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2 = 40% of the between-study heterogeneity for severity. The aforementioned covariates were found to be significant for mortality as well, and these covariates collectively explained R2 = 50% of the between-study variability for mortality.ConclusionsOur findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and improvement of guidelines for patient care management is recommended.

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Serum Complement C3 and C4 and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression.

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